Ahsfracf: This study was undertaken in order to determine the changes in auditory brainstem-evoked responses relationship with the changes in the levels of GSH, lipid peroxidation and antioxidant enzymes activity in cisplatin-induced ototoxicity and otoprotection by 4-methylthiobenzoic acid (MTBA). Male Wistar rats in different groups were treated as follows: 1) saline control; 2) cisplatin ( I 6 mg/kg. intraperitoneally); 3 ) MTBA (250 mg/kg, intraperitoneally), and 4) cisplatin plus MTBA. Post-treatment auditory brainstem-evoked responses were performed after three days and the rats were sacrificed and cochleae harvested. The cochleae were analyzed for glutathione (GSH), antioxidant enzyme activity, and malondialdehyde levels. The cisplatin injected rats showed a threshold elevation of 31.95 16.0 dB above the pretreatment thresholds using click stimulus. Rats treated with MTBA plus cisplatin did not show significant elevation of hearing threshold. Cisplatin plus MTBA administration showed a higher levels of cochlear GSH (5.59t0.35 nmoles/mg protein) compared to cisplatin alone (4.46?0. I3 nmolesimg protein). Cisplatin treated rats showed a decrease in superoxide dismutase, catalase, glutathione peroxidase (GSH-peroxidase), and glutathione reductase (GSH-reductase) activities (57"h. 83'%1, 78% and 58's of control). Cochlear superoxide dismutase, catalase and GSH-reductase activities and MDA levels were restored in the rats injected with cisplatin plus MTBA, compared to cisplatin alone. It is concluded that the protection conferred by MTBA against cisplatin ototoxicity is associated with sparing of the cochlear antioxidant system. Cisplatin (cis-diamminedichloroplatinum) is currently being used clinically as an effective antitumour agent against a variety of neoplasms, but its use is limited by the onset of side effects such as ototoxicity, nephrotoxicity, and peripheral neuropathy. High doses of cisplatin result in profound deafness (Rybak 1981; Fausti et al. 1984Fausti et al. & 1993Powis & Hacker 1991). The severity of these toxic side-effects remains an obstacle to the clinical use of high-dose cisplatin. To identify safer methods of cisplatin dose escalation, the use of chemoprotectors has been explored. al. 1992). procaine (Zhang et al. 1992), and other sulfur containing compounds (Basinger et al. 1990;Jones et al. 1991Jones et al. & 1992. The rationale for their use is the high affinity of sulfur ligands for platinum complexes.Clinical and experimental studies have demonstrated that administration of GSH is nephro-and neuroprotective but its role in otoprotection is unclear (Zunino P t al. 1989;Fontanelli et al. 1992;Hamers et a/. 1993 et ul. 1986;Zunino et a/. 1983;Hamers et al. 1993). However, the effect of GSH level in relation to ototoxicity is unknown.Ototoxicity is the dose-limiting side effect following diethyldithiocarbamate chemoprotection (Berry et 01. 1990). Preliminary results in clinical studies by Gandara et (11. (1990 & 1991) suggest possible protection against ototoxicity by diethyldit...

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